Strategy for Increasing Exports of Pharmaceutical Products

Strategy for Increasing Exports of Pharmaceutical Products 1. Introduction The pharmaceutical sector is one of India’s most important sectors in terms of projected revenue growth from exports and for meeting the needs of Indian population. There are a larger number of markets to which Indian pharmaceutical companies can now export as a result of global trade liberalisation and capacity building by Indian companies over the last decade. India, considered as a knowledge intensive economy, is looked upon to make available drugs that are affordable to the developing countries. The recent contribution of Indian generics in fighting AIDS and its contribution to affordable healthcare in US and elsewhere is widely acknowledged. 1.1 Mandate, Methodology and Analysis 1.1.1 Mandate Department of Commerce, Government of India decided to constitute a Task Force on pharmaceutical exports to suggest measures for boosting exports in a sustainable manner. Accordingly, a Task Force was constituted under the Chairmanship of Joint Secretary, Department of Commerce, incharge of Pharmaceutical exports, vide Office Order No.13/6/2006-EP (CAP), dated 18th July, 2006. The report of the task force has been delayed inordinately. The reasons are not far to seek. The mandate of the task force was as follows: (i) To examine the problems being faced by the exporters of pharmaceutical products in consultation with the stakeholders and to prepare short term, medium term and long term action plans. (ii) To review the progress of exports of pharmaceutical products and suggest measures of achieving the growth targets. (iii) To act as “Think tank” and make appropriate policy recommendations for boosting exports and generating more employment in the sector. (iv) To consult the trade and industry and identify policy and procedural bottlenecks and suggest ways to eliminate them. Report of the Task Force, Ministry of Commerce & Industry, December 12, 2008. 13 It was soon realised that an analysis of measures pertaining to foreign trade policy alone would have only touched the surface of the challenges facing a sector which has the greatest potential for growth. Moreover prospects of increasing exports are very intimately related to the challenges faced by the sector at home and unless some of them are examined, the committee would only have done partial justice to its mandate. The task force had a clear conviction about the connect between the domestic environment in which the sector works and its impact on export prospects. The last two terms of reference in any case required interaction with a wide cross section of the sector. This realisation led the task force to carry out a wider interaction with the stakeholders particularly with the experts in the industry and all this lead to unusually long time. Strategy for Increasing Exports of Pharmaceutical Products 1.1.2 Methodology The Task Force has primarily used consultative process in formulating this paper and the data for the same has been gathered through various structured and unstructured meetings among representatives of Department of Commerce, Government of India, Department of Chemicals and Petrochemicals including the newly constituted Department of Pharmaceuticals, Director General of Foreign Trade (DGFT), Department of Ayurved, Unani and Siddha medicine and various institutions such as Indian Drug Manufacturers Association (IDMA), Pharmaceutical Export Promotion Council (Pharmexcil), Ayurvedic Drug Manufacturers Association (ADMA), National Medicinal Plants Board (NMPB), etc., and various inputs, research reports and statistics provided by members of Pharmexcil, and other industry experts. In order to carry out consultations with industry experts many unstructured discussions were organised by the chairman of the task force and representatives from the industry have given wholehearted participation. Report of the Task Force, Ministry of Commerce & Industry, December 12, 2008. 14 This report seeks to discuss separately various segments of pharmaceutical industry such as Generic Pharmaceuticals, Contract Manufacturing, Drug Discovery and Contract Research Services and Indian System of Medicines because of the distinct nature of the problems that require to be addressed by each of these broad areas. Within each area, this report seeks to address, the challenges faced by domestic industry and suggest initiatives to be taken by Govt. of India. Whereas the report tries to address most of the issues which were brought before it by stakeholders and were considered significant by the taskforce, there is a likelihood of some of the issues having been missed out. In most cases it could be because of inter-se prioritisation leaving out the lesser of the issues to save on space and maintain the focus.

HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

The glossary will help you to understand the terminology in case you aren’t already familiar with the technique.

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HPLC	separation technique for components of organic mixtures involving retention of components on stationary phase packed inside column on the basis of physico – chemical interactions followed by sequential elution.
Stationary phase	solid bed inside column whose particles are coated with the retention phase
Mobile phase	liquid carrier medium used for transporting the sample through the HPLC system
Normal phase separation	separation mode in which the retention material is polar and mobile phase is nonpolar. Retained sample components are eluted in ascending order of polarity
Reverse phase separation	separation mode in which the stationary phase is nonpolar and mobile phase is polar. Elution order of components is in decreasing order of polarity.It is the most commonly used mode of HPLC separations.
Column efficiency	expressed in terms of HETP which expresses resolution power of the HPLC column.
Column	a steel tube packed with the stationary phase for separation of sample components
Autosampler	a device for automated precise selection and introduction of programmed sample volume into the HPLC system
Injector	manual or automated device capable of precise sample volume injection of sample into the HPLC system
Filter	frit fitted with a screen membrane to remove solid suspensions from mobile phase of sample
Degassing	procedure for removal of dissolved air from mobile phase using vacuum filtration, helium purging or online degassing

How Does High Performance Liquid Chromatography Work ?

The components of a basic high-performance liquid chromatography [HPLC] system are shown in the simple diagram in Figure E.

A reservoir holds the solvent [called the mobile phase, because it moves]. A high-pressure pump [solvent delivery system or solvent manager] is used to generate and meter a specified flow rate of mobile phase, typically milliliters per minute. An injector [sample manager or autosampler] is able to introduce [inject] the sample into the continuously flowing mobile phase stream that carries the sample into the HPLC column. The column contains the chromatographic packing material needed to effect the separation. This packing material is called the stationary phase because it is held in place by the column hardware. A detector is needed to see the separated compound bands as they elute from the HPLC column [most compounds have no color, so we cannot see them with our eyes]. The mobile phase exits the detector and can be sent to waste, or collected, as desired. When the mobile phase contains a separated compound band, HPLC provides the ability to collect this fraction of the eluate containing that purified compound for further study. This is called preparative chromatography [discussed in the section on HPLC Scale].

Note that high-pressure tubing and fittings are used to interconnect the pump, injector, column, and detector components to form the conduit for the mobile phase, sample, and separated compound bands.

Figure E: High-Performance Liquid Chromatography [HPLC] System

The detector is wired to the computer data station, the HPLC system component that records the electrical signal needed to generate the chromatogram on its display and to identify and quantitate the concentration of the sample constituents (see Figure F). Since sample compound characteristics can be very different, several types of detectors have been developed. For example, if a compound can absorb ultraviolet light, a UV-absorbance detector is used. If the compound fluoresces, a fluorescence detector is used. If the compound does not have either of these characteristics, a more universal type of detector is used, such as an evaporative-light-scattering detector [ELSD]. The most powerful approach is the use multiple detectors in series. For example, a UV and/or ELSD detector may be used in combination with a mass spectrometer [MS] to analyze the results of the chromatographic separation. This provides, from a single injection, more comprehensive information about an analyte. The practice of coupling a mass spectrometer to an HPLC system is called LC/MS.

Figure F: A Typical HPLC [Waters Alliance] System

HPLC Operation
A simple way to understand how we achieve the separation of the compounds contained in a sample is to view the diagram in Figure G.

Mobile phase enters the column from the left, passes through the particle bed, and exits at the right. Flow direction is represented by green arrows. First, consider the top image; it represents the column at time zero [the moment of injection], when the sample enters the column and begins to form a band. The sample shown here, a mixture of yellow, red, and blue dyes, appears at the inlet of the column as a single black band. [In reality, this sample could be anything that can be dissolved in a solvent; typically the compounds would be colorless and the column wall opaque, so we would need a detector to see the separated compounds as they elute.]

After a few minutes [lower image], during which mobile phase flows continuously and steadily past the packing material particles, we can see that the individual dyes have moved in separate bands at different speeds. This is because there is a competition between the mobile phase and the stationary phase for attracting each of the dyes or analytes. Notice that the yellow dye band moves the fastest and is about to exit the column. The yellow dye likes [is attracted to] the mobile phase more than the other dyes. Therefore, it moves at a faster speed, closer to that of the mobile phase. The blue dye band likes the packing material more than the mobile phase. Its stronger attraction to the particles causes it to move significantly slower. In other words, it is the most retained compound in this sample mixture. The red dye band has an intermediate attraction for the mobile phase and therefore moves at an intermediate speed through the column. Since each dye band moves at different speed, we are able to separate it chromatographically.

Figure G: Understanding How a Chromatographic Column Works – Bands

What Is a Detector?
As the separated dye bands leave the column, they pass immediately into the detector. The detector contains a flow cell that sees [detects] each separated compound band against a background of mobile phase [see Figure H]. [In reality, solutions of many compounds at typical HPLC analytical concentrations are colorless.] An appropriate detector has the ability to sense the presence of a compound and send its corresponding electrical signal to a computer data station. A choice is made among many different types of detectors, depending upon the characteristics and concentrations of the compounds that need to be separated and analyzed, as discussed earlier.

What Is a Chromatogram?
A chromatogram is a representation of the separation that has chemically [chromatographically] occurred in the HPLC system. A series of peaks rising from a baseline is drawn on a time axis. Each peak represents the detector response for a different compound. The chromatogram is plotted by the computer data station [see Figure H].

Figure H: How Peaks Are Created

In Figure H, the yellow band has completely passed through the detector flow cell; the electrical signal generated has been sent to the computer data station. The resulting chromatogram has begun to appear on screen. Note that the chromatogram begins when the sample was first injected and starts as a straight line set near the bottom of the screen. This is called the baseline; it represents pure mobile phase passing through the flow cell over time. As the yellow analyte band passes through the flow cell, a stronger signal is sent to the computer. The line curves, first upward, and then downward, in proportion to the concentration of the yellow dye in the sample band. This creates a peak in the chromatogram. After the yellow band passes completely out of the detector cell, the signal level returns to the baseline; the flow cell now has, once again, only pure mobile phase in it. Since the yellow band moves fastest, eluting first from the column, it is the first peak drawn.

A little while later, the red band reaches the flow cell. The signal rises up from the baseline as the red band first enters the cell, and the peak representing the red band begins to be drawn. In this diagram, the red band has not fully passed through the flow cell. The diagram shows what the red band and red peak would look like if we stopped the process at this moment. Since most of the red band has passed through the cell, most of the peak has been drawn, as shown by the solid line. If we could restart, the red band would completely pass through the flow cell and the red peak would be completed [dotted line]. The blue band, the most strongly retained, travels at the slowest rate and elutes after the red band. The dotted line shows you how the completed chromatogram would appear if we had let the run continue to its conclusion. It is interesting to note that the width of the blue peak will be the broadest because the width of the blue analyte band, while narrowest on the column, becomes the widest as it elutes from the column. This is because it moves more slowly through the chromatographic packing material bed and requires more time [and mobile phase volume] to be eluted completely. Since mobile phase is continuously flowing at a fixed rate, this means that the blue band widens and is more dilute. Since the detector responds in proportion to the concentration of the band, the blue peak is lower in height, but larger in width.

HEALTH BENEFITS OF DRINKING WARM WATER

When you drink a glass of warm water, fat deposits and toxins circulating in the blood are eliminated from the body. It also helps improve blood circulation in your body and lowers your risk of various health complications due to the presence of toxins in your blood. If you're on a diet, chances are you've heard drinking a glass of warm water first thing in the morning can help with weight loss. Warm water increases body temperature, which therefore increases the metabolic rate. An increase in metabolic rate allows the body to burn more calories throughout the rate. The good drinking a lot of water does to your body is, of course, clear now to every one. I drink about 2 liters of water daily, but not cold water. I hear drinking cold water will burn more calories as the body has to warm itself to room temperature when intaking the water into the system. It is a delicious and refreshing low-calorie natural beverage. Tender coconut water contains more nutrients than mature coconut water. It's packed with antioxidants, amino acids, enzymes, B-complex vitamins, vitamin C and minerals like iron, calcium, potassium, magnesium, manganese and zinc. Weight loss would be a breeze if a glass of hot water every morning did the trick. While this idea is too good to be true, drinking water at any temperature before meals could help some people eat less-- but it still doesn't guarantee weight loss. Water can be really helpful for weight loss. It is 100% calorie-free, helps you burn more calories and may even suppress your appetite if consumed before meals. ... However, keep in mind that you're going to have to do a lot more than just drink water if you need to lose a significant amount of weight. Improving digestion and immunity and acting as a natural skin lightening agent are a few health benefitsof lemons. It is believed that drinking the honey and lemon water mixture every morning on an empty stomach boosts metabolism which helps you lose weight.                                               

SKIN CARE PRODUCTS

Antiperspirants & Deodorants

About Antiperspirants

What are antiperspirants?

Antiperspirants are personal hygiene products designed to control sweating and body odour. Antiperspirants contain ingredients that control sweat and body odour safely and effectively. They are readily available on the market as sprays (aerosol), sticks, creams or roll-ons.

Is there a difference between an antiperspirant and a deodorant?¹

The terms ‘antiperspirant’ and ‘deodorant’ are often used interchangeably but they do in fact refer to different products. Antiperspirants control sweat and body odour (B.O.) in two ways: firstly by preventing sweat reaching the skin surface and secondly by reducing the bacteria that causes body odour via antimicrobial ingredients. Deodorants differ from antiperspirants as they only contain antimicrobial agents to prevent body odour; they do not control the flow of sweat. Both antiperspirants and deodorants often contain fragrances to help mask the smell of B.O.

How does an antiperspirant work?¹

When an antiperspirant is applied to the skin surface, its anti-perspirant ingredients – usually aluminium salts – dissolve in the sweat or moisture on the skin surface of the armpit. The dissolved substance forms a gel, which creates a small temporary ‘plug’ near the top of the sweat gland, significantly reducing the amount of sweat that is secreted to the skin surface. Bathing and washing will remove the antiperspirant gel. Re-application of antiperspirants can be beneficial to help reduce sweating and keep fresh throughout the day.  Antiperspirants reduce underarm sweating but they do not impact on the natural ability of the body to control its temperature (thermoregulation).

                                                                             

What ingredients are in antiperspirants and deodorants?  

Antiperspirants contain a number of ingredients to minimise sweating and help people feel fresh, cool and smelling good.

Alcohol is an ingredient present in some roll-ons, aerosols and gels. The active ingredients of antiperspirants and deodorants are often dissolved in alcohol because it dries quickly once applied to the skin and gives an immediate sense of coolness.

·         Aluminium salts²

Aluminium salts are the active ingredient in antiperspirants. They work to reduce the flow of sweat from the sweat gland to the skin surface. Aerosol and roll-on products are likely to contain aluminium chlorohydrate, whereas sticks, gels and other solid products are most likely to contain an aluminium salt called aluminium zirconium. These salts provide a safe and effective means of controlling sweat..

Aluminium chloride is a strong aluminium salt used to treat people with mild to moderate hyperhidrosis or excessive sweating [link]. Skin inflammation may occur as a side effect but this can be managed by following the product instructions carefully and using an emollient to protect the skin surface.³

Find out the difference between an antiperspirant and a deodorant 

Does aluminium in antiperspirants impact on health?  >>

·         Antimicrobials

The skin is home to natural bacteria that like to feed on sweat but as a result, produce bad smells. In occluded areas, such as the underarm, there are about 1 million bacteria per square centimetre.  By lowering the number of bacteria on the skin, body odour can also be reduced. Antimicrobials agents kill bacteria and also slow their growth so that you stay odour-free for longer.

Aluminium salts present in antiperspirants are natural antimicrobial agents so they also kill bacteria on your skin. High efficacy deodorants (without aluminium salts) are available and rely on the use of specifically developed antimicrobial agents, such as triclosan or polyhexamethylene biguanide.

Alcohol is also effective at killing bacteria so deodorant and antiperspirant products that contain alcohol (or ethanol) are able to reduce body odour by combating the odour-forming bacteria.

Soap and water is not completely effective at killing and removing bacteria from the underarm, which is why many people use an antiperspirant or deodorant as part of their daily routine to control body odour and sweating. 

·         Fragrance and skin conditioners²

Perfumes and fragrances are used in most deodorants and antiperspirants in order to mask body odour and provide a feeling of freshness to the user. Many antiperspirants products contain some emollient oils to soothe and soften the skin. In roll-ons and sticks, the oils also provide a 'gliding' feeling as the product is applied.

The moisturisers used in antiperspirants are usually glycerin or vegetable derived oils, such as sunflower oil (helianthus annus). Most antiperspirants will also contain an oil to stop the product drying out into deposits, thus minimising product residue on skin and clothes. Silica, a natural mineral, is also used in antiperspirants to absorb this oiliness so that the skin does not feel too greasy after application.

·         Carrier substances²

In order for antiperspirants to be effectively applied to the skin, they need to be held in some kind of carrying structure - whether that be the liquids used in aerosols or the solids used in sticks.  Water is used in a range of antiperspirants as a carrier for other ingredients as it adds fluidity to roll-ons and creams and helps the product spread onto the skin. In aerosol products the ingredients are held in a neutral liquid which enables them to be easily sprayed onto the skin. This liquid (commonly cyclomethicone) is often combined with a slightly denser mineral clay-like substance (disteardimonium hectorite) which provides structure to the antiperspirant and stops heavier ingredients sinking to the bottom.

Likewise, solid antiperspirant products contain an agent which provides structure and prevents the ingredients from separating out. This structure can be provided by a combination of ingredients including hydrogenated castor oil, glycerol fats (triglycerides) and stearyl alcohol.

                 Some antiperspirant products also include an ingredient called PEG-8 distearate, which makes it easier to wash the product off in the bath or shower at the end of the day.

Parabens²

Parabens are a type of preservative found in many personal care products. The vast majority of antiperspirants do not contain parabens because

antiperspirants are generally self-preserving.

·         Propellants²

Aerosol antiperspirants are designed to work via a thin film which is propelled onto the skin. To create this film, products contain low, medium and high

pressure propellants which produce a strong, but comfortable, spray to reach the skin. These propellants are commonly butane, isobutane and propane

MICROENCAPSULATION PROCESS

ABSTRACT

Microencapsulation is a process in which active substances are coated by extremely small capsules. It is a new technology that has been used in the cosmetics industry as well as in the pharmaceutical, agrochemical and food industries, being used in flavors, acids, oils, vitamins, microorganisms, among others. The success of this technology is due to the correct choice of the wall material, the core release form and the encapsulation method. Therefore, in this review, some relevant microencapsulation aspects, such as the capsule, wall material, core release forms, encapsulation methods and their use in food technology will be briefly discussed.

Key words: microcapsules; microencapsulation; controlled release

INTRODUCTION

Microencapsulation may be defined as the packaging technology of solids, liquid or gaseous material with thin polymeric coatings, forming small particles called microcapsule^.The polymer acts as a protective film, isolating the core and avoiding the effect of its inadequate exposure. This membrane dissolves itself through a specific stimulus, releasing the core in the ideal place or at the ideal time Microencapsulation has numerous applications in areas such as the pharmaceutical, agricultural, medical and food industries, being widely used in the encapsulation of essential oils, colorings, flavorings, sweeteners, microorganisms, among others.

Recently, the food industry has demonstrated increasingly complex formulations: as microorganisms in fermented meat; the addition of polyunsaturated fatty acids that are susceptible to auto-oxidation in milk, yogurts or ice creams; and the use of flavor compounds that are highly volatile in instant foods, which often can only be checked by microencapsulation.

Microencapsulation can serve as an effective means of creating foods that are not only a source of nutrients with sensory appeal but also a source of well-being and health for individuals, such as by increasing the level of calcium to prevent osteoporosis, using microorganism-produced lactic acid to decrease cholesterol and adding phenolic compounds to prevent heart problems.

In this review, some relevant aspects of microencapsulation, such as the capsule, wall material, core release forms, encapsulation methods and some of their uses in food technology will be briefly discussed.

Capsule

Generally, capsules can be classified according to their size: macrocapsules (>5,000μm), microcapsules (0.2 to 5,000μm) and nanocapsules (<0.2μm). In terms of their shape and construction, capsules can be divided into two groups: microcapsules and microspheres. Microcapsules are particles consisting of an inner core, substantially central, containing the active substance, which is covered with a polymer layer constituting the capsule membrane. Mononuclear and polynuclear microcapsules can be distinguished by whether the core is divided (FAVARO-TRINDADE et al., 2008).

In contrast, microspheres are matrix systems in which the core is uniformly dispersed and/or dissolved in a polymer network. Microspheres may be homogeneous or heterogeneous depending on whether the core is in the molecular state (dissolved) or in the form of particles (suspended), respectively.

Wall materials

The correct choice of the wall material is very important because it influences the encapsulation efficiency and stability of the microcapsule. The ideal wall material should have the following characteristics: not reactive with the core; ability to seal and maintain the core inside the capsule; ability to provide maximum protection to the core against adverse conditions; lack an unpleasant taste in the case of food applicability and economic viability.

According to FÁVARO-TRINDADE et al. (2008), most wall materials do not have all the desired properties; a common practice involves mixing two or more materials. Such materials can be selected from a wide variety of natural and synthetic polymers, including the following that we highlight: carbohydrates: starch, modified starches, dextrins, sucrose, cellulose and chitosan; gums: arabic gum, alginate and carrageenan; lipids: wax, paraffin, monoglycerides and diglycerides, hydrogenated oils and fats; inorganic materials: calcium sulfate and silicates; proteins: gluten, casein, gelatin and albumin.

Controlled core release

encapsulation should allow the core to be isolated from the external environment until release is desired. Therefore, the release at the appropriate time and place is an extremely important property in the encapsulation process, improving the effectiveness, reducing the required dose of additives and expanding the applications of compounds of interest. The main factors affecting the release rates are related to interactions between the wall material and the core. Additionally, other factors influence the release, such as the volatility of the core, ratio between the core and wall material, particle size and viscosity grade of the wall material.

The main mechanisms involved in the core release are diffusion, degradation, use of solvent, pH, temperature and pressure. In practice, a combination of more than one mechanism is used. Diffusion occurs especially when the microcapsule wall is intact; the release rate is governed by the chemical properties of the core and the wall material and some physical properties of the wall. For example, some acids can be released during a process step but protected by another step. In some cases, some preservatives are required at the product surface, but their spread to other parts must be controlled.

degradation release occurs when enzymes such as proteases and lipases degrade proteins or lipids, respectively. An example is reducing the time required for the ripening of cheddar cheese by 50% compared with the conventional ripening process.

In contact with a solvent, the wall material can dissolve completely, quickly releasing the core or start to expand, favoring release. For example, microencapsulation of coffee flavors improves the protection from light, heat and oxidation when in the dry state, but the core is released upon contact with water.

The pH release occurs because pH changes can result in alterations in the wall material solubility, enabling the release of the core. For example, probiotic microorganisms can be microencapsulated to resist the acid pH of the stomach and only be released in the alkaline pH of the intestine (TOLDRÁ & REIG, 2011).

Changes in temperature can promote core release. There are two different concepts: temperature-sensitive release, reserved for materials that expand or collapse when a critical temperature is reached, and fusion-activated release, which involves melting of the wall material due to temperature increase. An example is the fat-encapsulated cheese flavor used in microwave popcorn, resulting in the uniform distribution of the flavor: the flavor is released when the temperature rises to 57-90°C.

Pressure release occurs when a pressure is applied to the capsule wall, such as the release of some flavors during the mastication of chewing gum.,Some wall materials and the possible mechanisms for the microcapsules release are listed in table 1.

Table 1 - Wall materials and their potential release mechanisms 

Wall Materials	-----------------------------------------------Release Mechanisms-----------------------------------------------
	Mechanic	Thermal	Dissolution	Chemical
Soluble in water
Alginate	x		x
Carrageenan	x		x
Caseinate	x		x
Chitosan	x
Modified cellulose	x		x
Gelatin	x
Xanthan gum	x	x
Arabic gum	x	x
Latex	x		x
Starch	x		x
Insoluble in water
Ethylcellulose	x
Fatty alcohols	x	x		x
Fatty acids	x	x		x
Hydrocarbon resin	x	x
Mono, di and triacyl glycerol	x	x
Natural waxes	x	x
Polyethylene	x	x

Source: adapted from FAVARO-TRINDADE et al. (2008)

Some encapsulation methods

The choice of the most suitable method depends on the type of core, the application for the microcapsule, the size of the particles required, the physical and chemical properties of the core and the wall, the release mechanism required, the production scale and the cost. the main encapsulation methods are: spray drying, spray cooling, extrusion, coacervation, lyophilization and emulsification.

Spray drying:

This process involves the formation of an emulsion, solution or suspension containing the core and wall material, followed by nebulization in a drying chamber with circulating hot air. The water evaporates instantly in contact with the hot air, and the material encapsulates the core.  Atomization has some advantages over other methods: large equipment availability, possibility of employing a wide variety of encapsulating agents, potentially large-scale production, simple equipment, good efficiency, reduced storage and transport costs and low process cost. The main disadvantage of atomization is the production of non-uniformly sized materials (MADENE et al., 2006).

The spray drying technique is the most common microencapsulation method, has been used for decades to encapsulate mainly flavors, lipids, and pigments, but its use in thermo-sensitive products, such as microorganisms and essential oils, can be limited because the required high temperature causes volatilization and/or destruction of the product.

The sumac flavor has been successfully encapsulated by spray drying in sodium chloride in salted cookies, salads and crackers . microencapsulated cardamom oleoresin by spray drying in arabic gum, maltodextrin and modified starch, the results showing an increase in the oleoresin protection.   optimized the microencapsulation of probiotics in raspberry juice by spray drying in 91.15%. The encapsulation of lipids in potato starches, tapioca and corn by spray drying has been successful, with no interactions between the encapsulated and wall materials (DRUSCH et al., 2006).

Spray cooling:

 The spray cooling microencapsulation is based on the injection of cold air to allow solidification of the particle. Microparticles are produced from a mixture containing the core and wall material in droplets. This mixture is nebulized by an atomizer and enters a chamber in which air flows at low temperature. The reduction of temperature results in the solidification of the wall material, enabling the core to be encapsulated.

Spray cooling microencapsulation is considered the cheapest encapsulation technology by employing lower temperatures and with a high potential for scale-up. However, microparticles can present some disadvantages, including low encapsulation capacity and the expulsion of the core during storage. Spray cooling has been used to encapsulate mainly minerals and vitamins (RATHORE et al., 2013).

 The  microencapsulated tocopherols in a lipid matrix by the spray cooling with values of encapsulation efficiency greater than 90%.  The developed microcapsules by spray cooling that contained iron, iodine and vitamin A to fortify salt using oil hydrogenated palm. The microcapsules obtained were highly stable and no sensory differences were detected. The encapsulating agent maltodextrin was shown to be efficient to prevent the oxidation of linseed oil by spray cooling.

This method is based on a polysaccharide gel that immobilizes the core when in contact with a multivalent ion. Extrusion involves incorporating the core in a sodium alginate solution, followed by the mixture undergoing drop-wise extrusion via a reduced caliber pipette or syringe into a hardening solution, such as calcium chloride (SWARBRICK, 2004).

The main advantage of this process is the very long shelf life of flavor compounds due to the provision of an almost impermeable barrier against oxygen. One of the drawbacks of this technology is the rather large particles formed by extrusion (typically 500-1,000mm), which limit the use in applications where mouth-feel is a crucial factor. Additionally, a very limited range of wall materials is available for extrusion encapsulation.

 The microencapsulated L. acidophilus in a calcium alginate gel and resistant starch by extrusion, resulting in an increased survival rate of L. acidophilus in Iranian white-brined cheese after 6 months of storage. YULIANI et al. (2006) showed that the microencapsulation of limonene with β-cyclodextrin by extrusion offered an effective means against oxidation.

Coacervation:

Coacervation is the technique that involves the deposition of the polymer around the core by altering the physicochemical characteristics of the medium, such as the temperature, ionic strength, pH and polarity.It is called simple coacervation when only a single macromolecule is present, whereas when there are two or more molecules of opposite charges is referred to as complex coacervation (FREITAS et al., 2005).

Coacervation is a relatively simple, low-cost process that does not require high temperatures or organic solvents. It is typically used to encapsulate flavor oils . One of the main disadvantages of the coacervation is that occurs only within limited ranges of pH, colloid concentrations and/or electrolyte concentrations.

JUN-XIA et al. (2011) microencapsulated sweet orange oil by coacervation with soybean protein isolate, indicating good protection for the core.      microencapsulated B. lactis and L. acidophilus by coacervation with pectin and casein, demonstrating more resistance of the product to gastric and intestinal juices. ROCHA-SELMI et al. (2013) encapsulated aspartame by coacervation, improving the protection even at 80ºC.

Lyophilization:

Lyophilization is a method involving the dehydration of frozen material under a vacuum sublimation process, that is, compound water removal occurs without submitting the sample to high temperatures (CHEN & WANG, 2007).

This method provides excellent quality products because it minimizes the changes associated with high temperature, it is widely used in essences or flavorings. However, its high cost and long process time undermine its commercial applicability. CALVO et al. (2012) microencapsulated extra-virgin olive oil in the presence of maltodextrin, carboxymethylcellulose and lecithin by lyophilization, demonstrating that the oil was unaltered for 9 to 11 months, which increased the shelf life. encapsulated garcinia fruit extract in whey protein isolate and maltodextrin by lyophilization and aplicated in bread that exhibited higher volume, softer crumb texture, desirable colour and sensory attributes.

Emulsification:

In the microencapsulation by emulsification, first the core is dispersed in an organic solvent where the wall material is. Then, dispersion is emulsified in the water or oil, which contains an emulsion stabilizer. The organic solvent is then removed by evaporation under stirring, providing the formation of compact polymer globules in which the core is encapsulated.

This technique has been frequently used because of the simplicity of the procedures involved in producing the particle and the choice of the components of the formulation and preparation conditions. Emulsification has been used to encapsulate mainly enzymes, minerals, vitamins and microorganisms .             With the use of encapsulated enzymes by emulsification in cheese production, there was an increased rate of proteolysis compared with free enzyme production.    SONG et al. (2013) microencapsulated probiotics by emulsification in alginate-chitosan, demonstrating more resistance in simulated gastrointestinal conditions. Some encapsulation methods and their size ranges of the microcapsules are shown in table 2.

Table 2 - Encapsulation methods and sizes of capsules 

Encapsulation Methods	Core	Size (µm)
Physical Methods
Spray drying	Liquid/solid	5 - 150
Spray cooling	Liquid/solid	20 - 200
Fluidized bed	Solid	>100
Co-crystallization	Liquid/solid	-
Lyophilization	Liquid	-
Physicochemical Methods
Simple coacervation	Liquid/solid	20 - 500
Complex coacervation	Liquid/solid	1 - 500
Solvent evaporation	Liquid/solid	1 - 5,000
Liposomes	Liquid/solid	0.02 - 3

Source: adapted from FAVARO-TRINDADE et al. (2008)

CONCLUSION

Microencapsulation has been applied in a wide variety of products from different areas, and studies have shown an enormous potential to provide the core with advantageous features, resulting in superior quality products, including in the food industry. However, much effort through research and development is still needed to identify and develop new wall materials and to improve and optimize the existing methods of encapsulation for the better use of microencapsulation and its potential applications.